Patients with diabetes mellitus commonly develop complications of the gastrointestinal tract but the exact pathophysiologic mechanisms responsible for them are not well understood. Evidence exists to suggest that there are: 1) alterations in gastrointestinal motility; 2) disordered regulatory peptide control; and 3) a neuropathy of the autonomic nervous system in animals and patients with diabetes. The principal investigator presents data to show that rats with spontaneous diabetes have severe alterations of myoelectric activity of the small intestine. Recently, patients with diabetes have been shown to have similar abnormalities involving alterations of intestinal motility during fasting and fed states. Plasma concentrations of motolin and neurotensin appear to be responsible for the normal control of these motility patterns and abnormalities in the concentrations of these and other regulatory peptides have been observed in patients with diabetes. The principal investigator plans to evaluate myoelectric activity of the small intestine in a rat model with diabetes to determine how the extent of glycemic control and the duration of diabetes effects disturbances of intestinal motility. Alterations in motilin and neurotensin levels will be studied to determine whether there is a correlation between alterations in motility and these specific regulatory peptides. The physiologic ramifications of the alterations in motility will be assessed by analysing transit of the small intestine and determine whether bacterial overgrowth is present. In addition, the principal investigator has constructed studies to investigate the role of continuous insulin infusion and aldose reductase inhibitors in prophylaxis against, and as therapeutic agents in the treatment of gastrointestinal complications in diabetic animals.